Many plant species belonging to the family Labiatae (Lamiaceae) produce essential oils (aromatic oils) which are used as natural sources of insect repellent and fragrant chemicals [Hay, R. K. M. and Svoboda, K. P. Botany, In “Volatile Oil Crops: their biology, chemistry and production”; Hay, R. K. M., Waterman, P. G. (eds.); Longman Group UK Limited (1993)]. Plants of the genus Nepeta (catmints) are included as members of this family, and produce an essential oil which is a minor item of commerce. This oil is very rich in a class of monoterpenoid compounds known as iridoids [Inouye, H. Iridoids. Methods in Plant Biochemistry 7:99-143 (1991)], more specifically the methylcyclopentanoid nepetalactones [Clark, L. J. et al. The Plant Journal, 11:1387-1393 (1997)] and derivatives.
Four stereoisomers of nepetalactone are known to exist in nature, which may be readily obtained from different species within the plant genus Nepeta. These chemicals exert a well-known excitatory effect on cats [Tucker, A. O. and S. S. Tucker. Economic Botany 42: 214-231 (1988)], thus the oil—or more commonly, the dried herbage of this plant termed catnip—is used in cat toys. The leaves and oil of Nepeta spp. do not possess a particularly attractive aroma. The uses of the herbage and oil has therefore been confined to the small market offered by domestic cat toys and accessories. A small proportion of the oil of various Nepeta spp. consists of dihydronepetalactones, which are possibly derived biosynthetically from the more abundant nepetalactones [Regnier, F. E., et al. Phytochemistry 6:1281-1289 (1967); DePooter, H. L., et al. Flavour and Fragrance Journal 3:155-159 (1988); Handjieva, N. V. and S. S. Popov. J. Essential Oil Res. 8:639-643 (1996)].
Iridoid monoterpenoids have long been known to be effective repellents to a variety of insect species [Eisner, T. Science 146:1318-1320 (1964); Eisner, T. Science 148:966-968 (1965); Peterson, C. and J. Coats, Pesticide Outlook 12:154-158 (2001); and Peterson, C. et al. Abstracts of Papers American Chemical Society, (2001) 222 (1-2): AGRO73]. However, studies of the repellency of dihydronepetalactones have been much less conclusive [Cavill, G. W. K., and D. V. Clark. J. Insect Physiol. 13:131-135 (1967); Cavill, G. W. K., et al. Tetrahedron 38:1931-1938 (1982); Jefson, M., et al. J. Chemical Ecology 9:159-180 (1983)]. Recent studies have indicated that dihydronepetalactones may exert a repellent effect on the common insect pests of human society. Thus, a source of dihydronepetalactones (or a precursor) capable of supplying these compounds economically and in quantity may be required to allow commercial application of these molecules as insect repellents.
Additionally, it has been proposed that dihydronepetalactone compounds be used as fragrance materials. In view of these considerations, a source of dihydronepetalactones (or a precursor) capable of supplying these compounds economically and in quantity may also be required to allow commercial application of these molecules as fragrance materials.
Processes for hydrogenating iridoid monoterpene lactones (e.g., isoneonepetalactone, isodehydroiridomyrmecin, and isoactinidialactone) have been reported using platinum oxide (PtO2) catalyst [Sakai, T. et al. Bull. Chem. Soc. Jpn., 53(12): 3683-6 (1980)]. Likewise, neonepetalactone and isoneonepetalactone were hydrogenated with PtO2 in Et2O and with Raney Ni in ethanol [Sakai, T. et al. Koen Yoshishu—Koryo, Terupen oyobi Seiyu Kagaku ni kansuru Toronkai, 23rd (1979), 45-48; Publisher: Chem. Soc. Japan, Tokyo, Japan].
Using similar methodology, processes for producing dihydronepetalactones by hydrogenation of nepetalactone are described in Regnier, R. E. et al. [Phytochemistry 6:1281-1289 (1967)]. Specifically, nepetalactone was treated with hydrogen and platinum oxide (PtO2) catalyst to yield                53% methyl-2-isopropyl-5-methylcyclopentanecarboxylate,        2.8% α-dihydronepetalactone, and        35% δ-dihydronepetalactone.When a palladium catalyst supported on strontium carbonate (Pd/SrCO3) was used,        90% α-dihydronepetalactone,        3% methyl-2-isopropyl-5-methylcyclopentanecarboxylate, and a trace of δ-dihydronepetalactone was formed.Both of these strategies for hydrogenation are limited, however; PtO2 is an unsupported catalyst which permitted formation of a significant amount of open-ring derivatives, while SrCO3 is an expensive support.        
A need thus remains for an economical, efficient process for the production of dihydronepetalactones. The metals selected for use as catalysts in the process of this invention provide the desired economy and efficiency of production with a high degree of selectivity to the dihydronepetalactone product.